扰动单细胞转录组测序数据的肿瘤药物响应类型鉴定方法

By constructing a two-layer single-cell similarity network and graph embedding algorithm, the problem of accurate identification of drug response types in tumors was solved, achieving accurate identification and visualization of tumor drug response types, and revealing the dynamic changes of tumor cells and the state relationship under drug action.

CN118016166BActive Publication Date: 2026-07-17TSINGHUA UNIVERSITY

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
TSINGHUA UNIVERSITY
Filing Date
2024-02-04
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Existing technologies struggle to accurately identify primary drug resistance, acquired drug resistance, and sensitive drug response patterns in different cells within tumors. Furthermore, they fail to fully utilize the contextual information of paired samples, resulting in a complex interplay between drug response mechanisms and cellular state heterogeneity, making it difficult to accurately identify molecular changes caused by drug perturbation.

Method used

A two-layer single-cell similarity network was constructed, and the embedding vectors of tumor cells were obtained through a graph embedding algorithm. Cell subpopulations were aligned based on the migration probability matrix, and the abundance and state changes of cell subpopulations were quantitatively measured by relative abundance change, absolute abundance change, and state migration cost to identify the tumor drug response type.

Benefits of technology

It enables the systematic reconstruction of complex drug response processes in tumors at the cellular subpopulation level, accurately identifies tumor cell subpopulations with similar cell states and fates, and can identify acquired resistance, absolute primary resistance, relative primary resistance, or sensitivity. It provides a visualization method for dynamic changes in tumor number and state, and displays abundance changes such as cell proliferation, inhibition, and death.

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Abstract

本发明涉及肿瘤生物信息学技术领域,公开一种扰动单细胞转录组测序数据的肿瘤药物响应类型鉴定方法,包括:获取配对的用药组和对照组的单细胞转录组测序数据;构建双层单细胞相似性网络;基于双层图嵌入算法,得到用药组和对照组中每个肿瘤细胞的嵌入向量,并根据嵌入向量分别对用药组和对照组的肿瘤细胞进行聚类,识别具有相似细胞状态和细胞命运的肿瘤细胞亚群;基于转移概率矩阵,将用药组的细胞亚群与对照组的细胞亚群对齐;采用相对丰度变化、绝对丰度变化和状态迁移代价定量衡量细胞亚群的丰度和状态变化,并鉴定肿瘤药物响应类型。本发明能够在细胞亚群水平上系统解析肿瘤药物响应,对于深入理解肿瘤异质、动态的耐药模式具有重要价值。
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